Abstract: One of the most promising therapeutic approaches for clinical spinal cord injuries (SCI) is a form of activity-based rehabilitation known as body-weight supported step training. The fundamental concept underlying this approach is that the locomotor circuitry of the injured spinal cord remains responsive to the sensory inputs signaling loading of the limbs, limb movement and contact with the ground. While a proportion of spinal cord injured individuals respond well to training, many do not, emphasizing the need for a greater understanding of the process. Importantly, even those that respond well to training retain significant deficits especially when compared to the successful training in some animal models where the spinal cord is completely transected and training is initiated acutely (within a few weeks of injury). Unfortunately, the majority of training in the clinical setting is not initiated until several months after injury, primarily because current training strategies require the patients to stand on a treadmill in a body harness, a process that would compromise their acute medical care. We have hypothesized, based on findings from many laboratories, including our own, that early application of a simple but focused training strategy will fundamentally change the responsiveness of the spinal cord circuitry to more comprehensive training applied later, when other medical complications have declined. Over the past several years we have developed a number of unique training tools that we will use to test this hypothesis and to develop training strategies that could be translated for bedside use in the clinic. We have also established a model of immobilization, allowing us to mimic the lack of activity experienced by the majority of individuals with SCI thus providing a clinically relevant strategy where the experimental animals are treated more like we treat patients acutely after injury. We propose to use these models to answer the following specific questions: 1) Is there is a window of opportunity, post-injury, during which retraining of immobilized animals can be effective at improving functional recovery of locomotion? 2) What kinds of sensory input are necessary for optimal retraining? 3) Can simple and focused training strategies, applied acutely, improve the response of the spinal cord to more comprehensive training strategies applied at later time points? If successful, the results from these studies will have the potential to fundamentally change how we approach clinical rehabilitation post-SCI.